42 results on '"Rongying Ou"'
Search Results
2. LINC01063 functions as an oncogene in melanoma through regulation of miR-5194-mediated SOX12 expression
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Jiangmei, Xu, Rongying, Ou, Gang, Nie, Juan, Wen, Li, Ling, Laiming, Mo, Rui, Xu, Mingfen, Lv, Liang, Zhao, Wei, Lai, and Yunsheng, Xu
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Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cancer Research ,Skin Neoplasms ,Oncology ,Cell Movement ,Cell Line, Tumor ,Humans ,Oncogenes ,Dermatology ,Melanoma ,Cell Proliferation ,SOXC Transcription Factors - Abstract
Melanoma is one of the most aggressive skin cancers and a major cause of cancer-linked deaths worldwide. As the morbidity and mortality of melanoma are increasing, it is necessary to elucidate the potential mechanism influencing melanoma progression. Tumor tissues and adjacent normal tissues (5 cm away from tumors) from 22 melanoma patients at the I-II stage and 39 patients at the III-VI stage were acquired. The expression of LINC01063 in melanoma was estimated by quantitative PCR. Functional assays were employed to investigate the function of LINC01063 in melanoma. Mechanism assays were adopted to explore the mechanism of LINC01063. LINC01063 knockdown impeded melanoma cell proliferation, migration, invasion, and epithelial-mesenchymal transition as well as melanoma tumor growth. Mechanistically, LINC01063 acted as an miR-5194 sponge to upregulate SOX12 expression. Finally, LINC01063 was tested to facilitate the malignant behaviors of melanoma cells via targeting miR-5194/SOX12. LINC01063 was significantly upregulated in melanoma. Specifically, LINC01063 displayed a higher level in patients at an advanced stage or with metastasis than those at an early stage or without metastasis. Our study revealed the oncogenic effects of LINC01063 on melanoma cell/tumor growth and its molecular mechanism involving miR-5194/SOX12, which might support LINC01063 to be the potential prognostic or therapeutic biomarker against melanoma.
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- 2022
3. Exploiting the potential of extracellular vesicles as delivery vehicles for the treatment of melanoma
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Chongchao, Hou, Qiang, Wu, Lizhou, Xu, Rongwei, Cui, Rongying, Ou, Danyang, Li, and Yunsheng, Xu
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Histology ,Biomedical Engineering ,Bioengineering ,Biotechnology - Abstract
Melanoma, the most aggressive skin cancer that originated from genetic mutations in the melanocytes, is still a troublesome medical problem under the current therapeutic approaches, which include surgical resection, chemotherapy, photodynamic therapy, immunotherapy, biochemotherapy and targeted therapy. Nanotechnology has significantly contributed to the development of cancer treatment in the past few years, among which extracellular vesicles (EVs) are nanosized lipid bilayer vesicles secreted from almost all cells that play essential roles in many physiological and pathological processes. In terms of melanoma therapy, the unique physicochemical properties of EVs make them promising nanocarriers for drug transportation compared to other synthetic nanocarriers. Moreover, EVs can be further engineered to maximize their drug delivery potential. Herein, in this minireview, we gave a brief overview of EV-based drug delivery strategies for melanoma therapy, in which different therapeutics delivered via EVs were summarized. We also highlighted the current progress of the EV-based delivery platform for melanoma therapy in clinical trials. The obstacles to applying exosomes in clinical practice toward further translation of EVs melanoma therapy were also discussed at the end. In summary, EVs offer promising prospects for melanoma therapy, whilst the ways for unlocking EVs’ full potential in melanoma therapies should be further investigated by solving relevant issues which hamper EVs-based melanoma therapy translation in the future.
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- 2022
4. Hsa_circ_0048179 attenuates free fatty acid-induced steatosis via hsa_circ_0048179/miR-188-3p/GPX4 signaling
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Liang Zhao, Rongying Ou, Yi Ren, Ye Zhao, Wenjun Yang, Jinduo Zhao, Wen-Feng Li, and Yunsheng Xu
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Aging ,Palmitates ,Apoptosis ,Mitochondria, Liver ,GPX4 ,hsa_circ_0048179 ,miR-188-3p ,chemistry.chemical_compound ,medicine ,Humans ,Oil Red O ,Viability assay ,Membrane Potential, Mitochondrial ,chemistry.chemical_classification ,Reactive oxygen species ,Chemistry ,lipid accumulation ,non-alcoholic fatty liver disease ,Hep G2 Cells ,RNA, Circular ,Cell Biology ,Transfection ,Phospholipid Hydroperoxide Glutathione Peroxidase ,medicine.disease ,Molecular biology ,MicroRNAs ,Gene Expression Regulation ,Liver ,Hepatocytes ,Steatosis ,Reactive Oxygen Species ,Intracellular ,Research Paper ,Oleic Acid ,Signal Transduction - Abstract
Although circular RNAs (circRNAs) are known to play key roles in non-alcoholic fatty liver disease, much about their targets and mechanisms remains unknown. We therefore investigated the actions and mechanisms of hsa_circ_0048179 in an in vitro model of NAFLD. HepG2 cells were exposed to oleate/palmitate (2:1 ratio) for 24 h to induce intracellular lipid accumulation. Using CCK-8 assays, flow cytometry, fluorescence microscopy, western blotting, RT-qPCR, and Oil red O staining, we found that oleate/palmitate treatment reduced cell viability while increasing apoptosis and lipid accumulation in HepG2 cells. Levels of the antioxidant enzyme GPX4 were decreased in oleate/palmitate-treated HepG2 cells, and there were corresponding increases in reactive oxygen species and damage to mitochondrial cristae. Levels of hsa_circ_0048179 expression were also suppressed by oleate/palmitate treatment, and GPX4 levels were markedly increased in HepG2 cells following transfection with hsa_circ_0048179. Analysis of its mechanism revealed that hsa_circ_0048179 upregulated GPX4 levels by acting as a competitive “sponge” of miR-188-3p and that hsa_circ_0048179 attenuated oleate/palmitate-induced lipid accumulation in HepG2 cells by sponging miR-188-3p. Collectively, our findings suggest that hsa_circ_0048179 may play a key role in the pathogenesis of steatosis and may thus be a useful target for drug development.
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- 2020
5. Polysaccharide-Based Hydrogels for Wound Dressing: Design Considerations and Clinical Applications
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Rongwei, Cui, Luhan, Zhang, Rongying, Ou, Yunsheng, Xu, Lizhou, Xu, Xiao-Yong, Zhan, and Danyang, Li
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Histology ,integumentary system ,Biomedical Engineering ,Bioengineering ,Biotechnology - Abstract
Wound management remains a worldwide challenge. It is undeniable that patients with problems such as difficulties in wound healing, metabolic disorder of the wound microenvironment and even severely infected wounds etc. always suffer great pain that affected their quality of lives. The selection of appropriate wound dressings is vital for the healing process. With the advances of technology, hydrogels dressings have been showing great potentials for the treatment of both acute wounds (e.g., burn injuries, hemorrhage, rupturing of internal organs/aorta) and chronic wounds such as diabetic foot and pressure ulcer. Particularly, in the past decade, polysaccharide-based hydrogels which are made up with abundant and reproducible natural materials that are biocompatible and biodegradable present unique features and huge flexibilities for modifications as wound dressings and are widely applicable in clinical practices. They share not only common characteristics of hydrogels such as excellent tissue adhesion, swelling, water absorption, etc., but also other properties (e.g., anti-inflammatory, bactericidal and immune regulation), to accelerate wound re-epithelialization, mimic skin structure and induce skin regeneration. Herein, in this review, we highlighted the importance of tailoring the physicochemical performance and biological functions of polysaccharide-based hydrogel wound dressings. We also summarized and discussed their clinical states of, aiming to provide valuable hints and references for the future development of more intelligent and multifunctional wound dressings of polysaccharide hydrogels.
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- 2022
6. Circular RNA circLMO1 Suppresses Cervical Cancer Growth and Metastasis by Triggering miR-4291/ACSL4-Mediated Ferroptosis
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Rongying Ou, Shun Lu, Luhui Wang, Yebo Wang, Mingfen Lv, Tian Li, Yunsheng Xu, Jieqiang Lu, and Ren-shan Ge
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Cancer Research ,Oncology - Abstract
BackgroundA number of studies have demonstrated that circular RNA (circRNA) plays a critical role in tumorigenesis and tumor progression. However, the biological effects of most circRNAs on cervical cancer remain unclear. Hsa_circ_0021087 (thereafter named circLMO1) is a circRNA generated from the circularization of exon 2 and exon 3 of LIM Domain Only 1 (LMO1) and first identified as a tumor suppressor in gastric cancer. We aimed to identify the role of circLMO1 in cervical cancer progression.MethodsCircLMO1 was verified through qPCR and Sanger sequencing. The biological role of circLMO1 in regulating cervical cancer growth and metastasis was investigated both in vitro and in the nude mouse xenograft tumor model. The dual luciferase reporter assay and rescue experiment were conducted to evaluate the interactions among circLMO1, microRNA (miR)-4291, and acyl-CoA synthetase long chain family member 4 (ACSL4). The role of circLMO1 in regulating ferroptosis was assessed by analyzing lipid reactive oxygen species (ROS), and malonyl dialdehyde (MDA), and glutathione (GSH) content.ResultsThe level of circLMO1 was down-regulated in cervical cancer tissues and was associated with the International Federation of Gynecology and Obstetrics (FIGO) staging. Functionally, circLMO1 overexpression inhibited cervical cancer growth and metastasis both in vitro and in vivo, whereas circLMO1 depletion promoted cervical cancer cell proliferation and invasion. Mechanistically, circLMO1 acted as a competing endogenous RNA (ceRNA) by sponging miR-4192 to repress target gene ACSL4. CircLMO1 promoted cervical cancer cell ferroptosis through up-regulating ACSL4 expression. Overexpression of miR-4291 or knockdown of ACSL4 reversed the effect of circLMO1 on facilitating ferroptosis and repressing cervical cancer cell proliferation and invasion.ConclusionCircLMO1 acted as a tumor suppressor of cervical cancer by regulating miR-4291/ACSL4-mediated ferroptosis, and could be a promising biomarker for the clinical management of cervical cancer.
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- 2022
7. Circular RNA circLMO1 Suppresses Cervical Cancer Growth and Metastasis by Triggering miR-4291
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Rongying, Ou, Shun, Lu, Luhui, Wang, Yebo, Wang, Mingfen, Lv, Tian, Li, Yunsheng, Xu, Jieqiang, Lu, and Ren-Shan, Ge
- Abstract
A number of studies have demonstrated that circular RNA (circRNA) plays a critical role in tumorigenesis and tumor progression. However, the biological effects of most circRNAs on cervical cancer remain unclear. Hsa_circ_0021087 (thereafter named circLMO1) is a circRNA generated from the circularization of exon 2 and exon 3 of LIM Domain Only 1 (CircLMO1 was verified through qPCR and Sanger sequencing. The biological role of circLMO1 in regulating cervical cancer growth and metastasis was investigated bothThe level of circLMO1 was down-regulated in cervical cancer tissues and was associated with the International Federation of Gynecology and Obstetrics (FIGO) staging. Functionally, circLMO1 overexpression inhibited cervical cancer growth and metastasis bothCircLMO1 acted as a tumor suppressor of cervical cancer by regulating miR-4291/
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- 2022
8. FLT3L and granulocyte macrophage colony-stimulating factor enhance the anti-tumor and immune effects of an HPV16 E6/E7 vaccine
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Zhenzhen Ding, Rongying Ou, Liang Zhao, Laiming Mo, Xiangyun Li, Hua Zhu, Yunsheng Xu, Yi Ren, Rui Xu, and Tian Li
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Aging ,Papillomavirus E7 Proteins ,HPV16 vaccine ,Lymphocyte ,Uterine Cervical Neoplasms ,Spleen ,Granulocyte ,Cancer Vaccines ,Mice ,Adjuvants, Immunologic ,In vivo ,medicine ,Animals ,Macrophage ,Cytotoxic T cell ,Papillomavirus Vaccines ,Human papillomavirus 16 ,biology ,business.industry ,Granulocyte-Macrophage Colony-Stimulating Factor ,Membrane Proteins ,GM-CSF ,Oncogene Proteins, Viral ,Cell Biology ,Mice, Inbred C57BL ,Repressor Proteins ,FLT3L ,medicine.anatomical_structure ,Granulocyte macrophage colony-stimulating factor ,biology.protein ,Cancer research ,Female ,Antibody ,business ,Research Paper ,medicine.drug - Abstract
HPV16 infections promote the development and progression of cervical cancer. We investigated Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor as new adjuvants to an HPV16 vaccine. C57BL/6 mice were immunized by intramuscular injections of HPV16 E6/E7 plasmids every two weeks, three times in all. An in vivo imaging system was used to observe tumor growth and metastasis. Pathological changes to the heart, liver, spleen, lungs, brain and kidneys were recorded, and the survival rate of the mice was determined. The constructed HPV16 E6/E7 vaccine had no notable side effects in terms of physiological or biochemical indexes. Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor increased the inhibitory effects of the HPV16 E6/E7 vaccine on tumor growth and metastasis in vivo. The HPV16 E6/E7 vaccine enhanced the survival of mice and increased their serum-specific antibody and interferon-γ levels. Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor augmented these effects. In a cytotoxic lymphocyte killing test, Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor improved the ability of splenic lymphocytes from HPV16 E6/E7-vaccinated mice to kill B16 cells. As Fms-like Tyrosine Kinase 3 Ligand and granulocyte macrophage colony-stimulating factor enhanced the anti-tumor and immune effects of the HPV16 vaccine, these adjuvants should be considered for the treatment of cervical cancer.
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- 2019
9. Exosome-driven liquid biopsy for breast cancer: Recent advances in isolation, biomarker identification and detection
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Junjie Zhao, Lizhou Xu, Dongjie Yang, Huijing Tang, Yalin Chen, Xunzhi Zhang, Yunsheng Xu, Rongying Ou, and Danyang Li
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- 2022
10. Hydrogel-By-Design: Smart Delivery System for Cancer Immunotherapy
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Danyang Li, Rongying Ou, Yunsheng Xu, Rongwei Cui, Qiang Wu, Xiaoming Zheng, Jing Wang, and Shuxin Qu
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Histology ,immunomodualtors ,medicine.medical_treatment ,Biomedical Engineering ,Bioengineering ,Review ,02 engineering and technology ,03 medical and health sciences ,immune cells ,environmental regulatory substance ,Immune system ,Cancer immunotherapy ,Medicine ,hydrogels ,030304 developmental biology ,0303 health sciences ,cancer immunotherapy ,business.industry ,technology, industry, and agriculture ,Bioengineering and Biotechnology ,Immunotherapy ,021001 nanoscience & nanotechnology ,Precision medicine ,Targeted drug delivery ,Drug delivery ,Self-healing hydrogels ,Cancer research ,smart delivery ,0210 nano-technology ,business ,Adjuvant ,TP248.13-248.65 ,Biotechnology - Abstract
Immunotherapy has emerged as a promising strategy for cancer treatment, in which durable immune responses were generated in patients with malignant tumors. In the past decade, biomaterials have played vital roles as smart drug delivery systems for cancer immunotherapy to achieve both enhanced therapeutic benefits and reduced side effects. Hydrogels as one of the most biocompatible and versatile biomaterials have been widely applied in localized drug delivery systems due to their unique properties, such as loadable, implantable, injectable, degradable and stimulus responsible. Herein, we have briefly summarized the recent advances on hydrogel-by-design delivery systems including the design of hydrogels and their applications for delivering of immunomodulatory molecules (e.g., cytokine, adjuvant, checkpoint inhibitor, antigen), immune cells and environmental regulatory substances in cancer immunotherapy. We have also discussed the challenges and future perspectives of hydrogels in the development of cancer immunotherapy for precision medicine at the end.
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- 2021
11. Tryptophan 2, 3‑dioxygenase promotes proliferation, migration and invasion of ovarian cancer cells
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Qin He, Xiaoxiao Cheng, Kai-Fu Tang, Rongying Ou, Yunsheng Xu, Jiayu Jiang, Lina Chen, Yuemei Zhao, Shouhui Zhong, Jizao Du, Xiaoli Wu, Fengxing Tao, and Wei Chen
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0301 basic medicine ,Cancer Research ,Carcinogenesis ,proliferation ,Cell ,tryptophan 2,3-dioxygenase ,Carcinoma, Ovarian Epithelial ,Biology ,migration ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Molecular Biology ,Kynurenine ,Cell Proliferation ,Ovarian Neoplasms ,Gene knockdown ,Oncogene ,Cell growth ,Cancer ,Articles ,Cell cycle ,invasion ,medicine.disease ,Molecular medicine ,Tryptophan Oxygenase ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,ovarian cancer ,Cell Transformation, Neoplastic ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Female ,Ovarian cancer - Abstract
Tryptophan 2,3‑dioxygenase (TDO2) is a key rate‑limiting enzyme in the kynurenine pathway and promotes tumor growth and escape from immune surveillance in different types of cancer. The present study aimed to investigate whether TDO2 serves a role in the development of ovarian cancer. Reverse transcription‑quantitative PCR and western blotting were used to detect the expression of TDO2 in different cell lines. The effects of TDO2 overexpression, TDO2 knockdown and TDO2 inhibitor on ovarian cancer cell proliferation, migration and invasion were determined by MTS, colony formation and Transwell assays. The expression of TDO2 in ovarian cancer tissues, normal ovarian tissues and fallopian tube tissues were analyzed using the gene expression data from The Cancer Genome Atlas and Genotype‑Tissue Expression project. Immune cell infiltration in cancer tissues was evaluated using the single sample gene set enrichment analysis algorithm. The present study found that RasV12‑mediated oncogenic transformation was accompanied by the upregulation of TDO2. In addition, it was demonstrated that TDO2 was upregulated in ovarian cancer tissues compared with normal ovarian tissues. TDO2 overexpression promoted proliferation, migration and invasion of ovarian cancer cells, whereas TDO2 knockdown repressed these phenotypes. Treatment with LM10, a TDO2 inhibitor, also repressed the proliferation, migration and invasion of ovarian cancer cells. The present study indicated that TDO2 can be used as a new target for the treatment of ovarian cancer.
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- 2021
12. MicroRNA-664 suppresses the growth of cervical cancer cells via targeting c-Kit
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Qianwen Zhang, Keyu Wang, Rongying Ou, Fan Lin, Xiangyun Li, Mingfen Lv, and Yunsheng Xu
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0301 basic medicine ,Pharmacology ,Cervical cancer ,biology ,Chemistry ,Cyclin D ,Pharmaceutical Science ,Cancer ,medicine.disease ,medicine.disease_cause ,Reverse transcription polymerase chain reaction ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Cell culture ,Apoptosis ,030220 oncology & carcinogenesis ,Drug Discovery ,microRNA ,medicine ,Cancer research ,biology.protein ,Carcinogenesis - Abstract
Background Cervical cancer is the second most common malignant cancer in women worldwide. Evidence indicated that miR-664 was significantly downregulated in cervical cancer. However, the mechanisms by which miR-664 regulates the tumorigenesis of cervical cancer remain unclear. Thus, this study aimed to investigate the role of miR-664 in cervical cancer. Methods Quantitative reverse transcription polymerase chain reaction was used to detect the level of miR-664 in tumor tissues and cell line. The dual luciferase reporter system assay and Western blotting were used to explore the interaction of miR-664 and c-Kit in cervical cancer. Results The expression of miR-664 in patients with cervical cancer was dramatically decreased compared with that in adjacent tissues. MiR-664 mimics significantly inhibited proliferation in SiHa cells via inducing apoptosis. In addition, miR-664 mimics induced apoptosis in SiHa cells via increasing the expressions of Bax and active caspase 3 and decreasing the level of Bcl-2. Moreover, dual-luciferase assay showed that c-Kit was the directly binding target of miR-664 in SiHa cells; overexpression of miR-664 downregulated the expression of c-Kit. Meanwhile, upregulation of miR-664 significantly decreased the levels of c-Myc and Cyclin D in cells. Furthermore, miR-664 markedly inhibited tumor growth of cervical cancer in xenograft. Conclusion Our data indicated that miR-664 exerted antitumor effects on SiHa cells by directly targeting c-Kit in vitro and in vivo. Therefore, miR-664 might be a potential therapeutic target for the treatment of patients with cervical cancer.
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- 2019
13. HPV16 E6 oncoprotein-induced upregulation of lncRNA GABPB1-AS1 facilitates cervical cancer progression by regulating miR-519e-5p/Notch2 axis
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Xiangyun Li, Jiangmin Lv, Yi Ren, Jianrong Li, Rongying Ou, Xuan Liu, Mingfen Lv, Wenfeng Li, Ye Zhao, Jinduo Zhao, Liang Zhao, and Yunsheng Xu
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0301 basic medicine ,Male ,Microarray ,Uterine Cervical Neoplasms ,Biology ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Downregulation and upregulation ,In vivo ,Cell Movement ,Cell Line, Tumor ,microRNA ,Genetics ,Animals ,Humans ,Receptor, Notch2 ,Neoplasm Metastasis ,Molecular Biology ,Cell Proliferation ,Messenger RNA ,Human papillomavirus 16 ,Mice, Inbred BALB C ,Oncogene ,Competing endogenous RNA ,Carcinoma ,Oncogene Proteins, Viral ,Middle Aged ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Cell culture ,Cancer research ,Female ,RNA, Long Noncoding ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Human papillomaviruses 16 (HPV16) is the primary causative agent of cervical cancer (CC). E6 oncoprotein plays a crucial role in cervical carcinogenesis and commonly cause the dysregulation of the long noncoding RNAs (lncRNAs) expression. However, the biological function of lncRNAs in HPV16-related CC remains largely unexplored. In the present study HPV16 E6-induced differential expression of lncRNAs, miRNA, and mRNA were identified using microarray-based analysis and verified in tumor r cell lines and tumor tissues, and the function of lncRNA in CC was investigated in vitro and in vivo. We found that an lncRNA, named GABPB1-AS1, was significantly upregulated in HPV16-positive CC tissues and cell lines. GABPB1-AS1 expression in HPV16-positive CC tissues was positively associated with tumor size, lymph node metastasis, and FIGO stage. High expression of GABPB1-AS1 was correlated with a poor prognosis for HPV16-positive CC patients. Functionally, E6-induced GABPB1-AS1 overexpression facilitated CC cells proliferation and invasion in vitro and in vivo. Mechanistically, GABPB1-AS1 acted as a competing endogenous RNA (ceRNA) by sponging miR-519e-5p, resulting in the de-repression of its target gene Notch2 which is well known as an oncogene. Therefore, GABPB1-AS1 functioned as a tumor activator in CC pathogenesis by binding to miR-519e-5p and destroying its tumor suppressive function. Collectively, current results demonstrate that GABPB1-AS1 is associated with CC progression, and may be a promising biomarker or target for the clinical management of CC.
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- 2020
14. MicroRNA-34a promotes MICB expression in hepatocytes
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Heng-Chao Zhang, Zhechao Zhang, Rongying Ou, Xiao Chen, Chunming Zhao, Xiaoli Wu, Wen-Jie Huang, Hongyan Lou, Shanshan Hu, Hui Liu, Meng-Tao Zhou, Lin-Jie Wei, Guiling Li, De-Wei Li, Yunsheng Xu, Kai-Fu Tang, and Wenjun Yang
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0301 basic medicine ,Cancer Research ,Carcinoma, Hepatocellular ,Carcinogenesis ,Down-Regulation ,Ataxia Telangiectasia Mutated Proteins ,Major histocompatibility complex ,Interferon-gamma ,03 medical and health sciences ,Cell Line, Tumor ,microRNA ,Humans ,Medicine ,E2F1 ,Protein kinase A ,Regulation of gene expression ,biology ,business.industry ,Histocompatibility Antigens Class I ,Liver Neoplasms ,Cancer ,Hep G2 Cells ,Oncogenes ,General Medicine ,medicine.disease ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Killer Cells, Natural ,MicroRNAs ,030104 developmental biology ,MicroRNA 34a ,Ataxia-telangiectasia ,Hepatocytes ,Cancer research ,biology.protein ,business ,E2F1 Transcription Factor - Abstract
MicroRNA-34a (miR-34a) behaves as a tumor suppressor by decreasing the expression of oncogenes involved in multiple carcinogenic pathways. Intravenous delivery of miR-34a mimics has been investigated in clinical trials as a potential treatment for advanced cancers; however, the effect of miR-34a on cancer immune surveillance is controversial. In the current study, we found that miR-34a plays a dual role in the regulation of major histocompatibility complex class I-related sequence B (MICB) protein, a ligand of the NKG2D receptor. MiR-34a could both induce and reduce MICB expression by upregulating ataxia telangiectasia and Rad3-related (ATR) protein kinase and downregulating the transcription factor E2F1, respectively. The net effect of miR-34a on MICB expression depended on endogenous E2F1 levels. Overexpression of miR-34a promoted MICB expression in hepatocytes and hepatocellular carcinoma (HCC) cells that have low E2F1 levels but not in HCC cells that have high E2F1 levels. In HCC patients, the expression of miR-34a and MICB showed positive correlation in paratumor liver tissues, which have low E2F1 levels, but not in HCC tissues, which have high E2F1 levels. We showed that miR-34a overexpression in non-transformed liver cells enhanced cytolysis and interferon-γ production by NK-92MI cells. Furthermore, higher miR-34a expression in tumor and paratumor tissues was associated with positive and negative outcomes, respectively, in HCC patients. Our findings suggest that miR-34a induces MICB expression in paratumor liver tissues, which may cause liver damage and serious cytokine release syndrome, thus disclosing potential side effects of systemic administration of miR-34a in anticancer therapy.
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- 2018
15. HPV16 E7‐induced upregulation of KDM2A promotes cervical cancer progression by regulating miR‐132–radixin pathway
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Linyu Zhu, Yiyi Lu, Jianrong Li, Yi Ren, Rongying Ou, Fengxing Tao, Wenfeng Li, Liang Zhao, Yunsheng Xu, and Qin He
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Transcriptional Activation ,0301 basic medicine ,Jumonji Domain-Containing Histone Demethylases ,Physiology ,Clinical Biochemistry ,Uterine Cervical Neoplasms ,KDM2A ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Radixin ,Cell Line, Tumor ,Histone methylation ,microRNA ,Humans ,Medicine ,Epigenetics ,Promoter Regions, Genetic ,Cell Proliferation ,Cervical cancer ,biology ,business.industry ,F-Box Proteins ,Papillomavirus Infections ,Membrane Proteins ,Cell Biology ,medicine.disease ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Cytoskeletal Proteins ,MicroRNAs ,030104 developmental biology ,Tumor progression ,030220 oncology & carcinogenesis ,Disease Progression ,biology.protein ,Cancer research ,Female ,business - Abstract
Background Human papillomavirus (HPV) infection and viral proteins expression cause a number of epigenetic alterations leading to cervical carcinogenesis. The recent discovery of a large amount of histone methylation modifiers reveals important roles of these enzymes in regulating tumor progression. Methods The changes in expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E7 in CaSki cells. Lysine-specific demethylase 2A (KDM2A)-regulated microRNAs (miRNAs) in cervical cancer pathogenesis were disclosed using quantitative real-time polymerase chain reaction. The function of KDM2A-miRNAs on cervical cancer was investigated in vitro and in vivo. Results Upregulation of KDM2A induced by HPV16 E7 promotes cervical cancer cell proliferation and invasion and is correlated with poor prognosis in patients with cervical cancer. KDM2A physically interacts with the promoter of miR-132 and suppresses its expression by removing the mono or dimethyl group from H3K36 at the miR-132 locus. Functionally, miR-132 represses cancer cell proliferation and invasion by inhibiting radixin (RDX). Upregulated KDM2A promotes cervical cancer progression by repressing miR-132, which results in a derepression of RDX. Therefore, KDM2A functions as a tumor activator in cervical cancer pathogenesis by binding miR-132 promoter and abrogating its tumor suppressive function. Conclusion Our results suggest a function for KDM2A in cervical cancer progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of cervical cancer.
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- 2018
16. Upregulation of the ALDOA/DNA-PK/p53 pathway by dietary restriction suppresses tumor growth
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Meng-Tao Zhou, Kai-Fu Tang, Xiaoming Chen, Heng-Chao Zhang, Tang Jz, Rongying Ou, Lin-Jie Wei, Di Ma, Hu S, Xie C, Yunsheng Xu, and Pei-Ying Zhang
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0301 basic medicine ,Cancer Research ,Carcinoma, Hepatocellular ,Mice, Nude ,Apoptosis ,DNA-Activated Protein Kinase ,Mice ,03 medical and health sciences ,Downregulation and upregulation ,Cell Movement ,Fructose-Bisphosphate Aldolase ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Genetics ,Animals ,Humans ,Neoplasm Invasiveness ,Protein kinase A ,Molecular Biology ,Caloric Restriction ,Cell Proliferation ,Mice, Inbred BALB C ,biology ,Oncogene ,Cell growth ,Liver Neoplasms ,Aldolase A ,Nuclear Proteins ,Xenograft Model Antitumor Assays ,Molecular biology ,Diet ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,biology.protein ,Phosphorylation ,Female ,Tumor Suppressor Protein p53 ,Signal transduction - Abstract
Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.
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- 2017
17. Exploration of bladder cancer molecular mechanisms based on miRNA-mRNA regulatory network
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Li Zhu, Di Zou, Jingying Wang, Rongying Ou, Yunsheng Xu, Liang Zhao, Jia Liu, Xiaye Cai, Jinmeng Wang, and Wenfeng Li
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0301 basic medicine ,Cancer Research ,Biology ,Real-Time Polymerase Chain Reaction ,Bioinformatics ,medicine.disease_cause ,Aldehyde Dehydrogenase 1 Family ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,Humans ,Gene Regulatory Networks ,RNA, Messenger ,Bladder cancer ,Oncogene ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Retinal Dehydrogenase ,Cancer ,General Medicine ,Aldehyde Dehydrogenase ,medicine.disease ,Molecular medicine ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,MicroRNAs ,030104 developmental biology ,Urinary Bladder Neoplasms ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Carcinogenesis - Abstract
To explore the complex molecular mechanisms of bladder cancer, mRNA and miRNA expression profiles were combined for systematic analyses. A total of 18 common differentially expressed genes (DEGs) were identified from two mRNA expression datasets which consisted of 206 tumor and 74 normal tissues. Then, survival analysis based on the SurvExpress database showed that the common DEGs were able to significantly differentiate low- and high-risk groups in 4 public bladder cancer datasets (p
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- 2017
18. Flt3L and GM-CSF enhance anti-tumor effect of HPV16/18 vaccine via increasing immune response
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Yu, Liu, Haiyan, Zhu, Laiming, Mo, Rui, Xu, Xiangyun, Li, Tian, Li, Liang, Zhao, Yi, Ren, Rongying, Ou, and Yunsheng, Xu
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Original Article - Abstract
Objectives: Cervical cancer is the second leading cause of cancer death in women, which is closely related to persistent infection with high-risk Human papillomavirus (HPV). Therefore, it is important to develop new adjuvants for HPV vaccines. This research aimed to establish two new adjuvants which can enhance the immune effect of vaccines. Materials and Methods: C57BL/6 mice were divided into 5 groups and immunized by intramuscular injection of plasmid once every 2 weeks, three times in all. The growth and metastasis of tumors in mice was observed by in vivo imaging system (IVIS). Then, the mice were sacrificed and the pathological changes of organs were observed. In addition, the lymphocyte suspension was used for CLT killing test. IFN-γ level and the number of splenocytes which secrete IFN-γ were detected. Additionally, the specific antibody level of HPV16/18 E6 E7 L1 L2 was also detected. Results: The constructed nucleic acid vaccines had no significant effect on both the physiological and biochemical indexes, while it significantly increased the survival period and survival rate of mice. Flt3L and GM-CSF enhanced the immune effect of HPV16/18 vaccine via increasing the specific antibodies and IFN-γ cytokines. Conclusions: These data suggested that Flt3L and GM-CSF enhanced the anti-tumor effect of vaccines via increasing immune response. Thereby, our findings may hope to provide new perspective for the treatment of cervical cancer.
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- 2019
19. miR‑146a regulates the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑κB signaling by targeting TRAF6
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Mengxiong Li, Xiaoyu Xu, Tian Li, Jie Ding, Chengfang Xu, Li Cheng, and Rongying Ou
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0301 basic medicine ,Cancer Research ,Cellular differentiation ,Cell ,Uterine Cervical Neoplasms ,Apoptosis ,Biology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,medicine ,Humans ,Aged ,Cell Proliferation ,TNF Receptor-Associated Factor 6 ,Oncogene ,Cell growth ,Intracellular Signaling Peptides and Proteins ,NF-kappa B ,Cancer ,Cell Differentiation ,General Medicine ,Middle Aged ,Cell cycle ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Cancer research ,Th17 Cells ,Female ,Signal Transduction - Abstract
The aim of the present study was to investigate whether miRNA‑146a regulated the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis. miR‑146a expression was increased in human cervical cancer. Both overall survival (OS) and disease‑free survival (DFS) of low miR‑146a expression were higher than those of high miR‑146a expression. Additionally, IL‑17a expression was lower in patients with high miR‑146a expression compared to that of patients with lower miR‑146a expression. In a co‑culture of cervical cancer and CD4+ T cells, downregulation of miR‑146a inhibited cell growth and induced apoptosis of cervical cancer cells, while overexpression of miR‑146a promoted cell growth and reduced apoptosis of cervical cancer cells. Downregulation of miR‑146a induced TRAF6 and NF‑κB protein expression, increased IL‑6, IL‑17A and IL‑21 levels, and enhanced p‑STAT3 protein expression. The inhibition of TRAF6 attenuated the effects of anti‑miR‑146a on the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis. Collectively, miR‑146a regulated the function of Th17 cell differentiation to modulate cervical cancer cell growth and apoptosis through NF‑κB signaling by targeting TRAF6. miR‑146a may function as an oncogene in cervical cancer via Th17 cell differentiation by targeting TRAF6.
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- 2019
20. Additional file 2: of Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology
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Chen, Xiao, Liu, Mi, Hongyan Lou, Yiyi Lu, Zhou, Meng-Tao, Rongying Ou, Yunsheng Xu, and Tang, Kai-Fu
- Abstract
Contains all full-length western blot images. (PDF 720 kb)
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- 2019
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21. Additional file 1: of Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology
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Chen, Xiao, Liu, Mi, Hongyan Lou, Yiyi Lu, Zhou, Meng-Tao, Rongying Ou, Yunsheng Xu, and Tang, Kai-Fu
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Contains supplementary methods, supplementary tables, and eight supplementary figures with legends. (PDF 1250 kb)
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- 2019
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22. Additional file 3: of Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology
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Chen, Xiao, Liu, Mi, Hongyan Lou, Yiyi Lu, Zhou, Meng-Tao, Rongying Ou, Yunsheng Xu, and Tang, Kai-Fu
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Review history. (DOCX 744 kb)
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- 2019
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23. Retracted Article: The nuclear export of TR3 mediated gambogic acid-induced apoptosis in cervical cancer cells through mitochondrial dysfunction
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Jia Liu, Chunhong Zhang, Liang Zhao, Fengxing Tao, Qin He, Yiyi Lu, Rongying Ou, Wenfeng Li, and Yunsheng Xu
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Cervical cancer ,Chemotherapy ,Chemistry ,General Chemical Engineering ,medicine.medical_treatment ,General Chemistry ,Drug resistance ,medicine.disease ,chemistry.chemical_compound ,Apoptosis ,Cervical carcinoma ,Cancer research ,medicine ,Cytotoxic T cell ,Gambogic acid ,Nuclear export signal - Abstract
At present, chemotherapy is still the main treatment for cervical cancer. However, the drug resistance of chemotherapy drugs seriously restricts its use, so it is urgent to develop new drugs for cervical cancer. Some studies have shown that gambogic acid has a strong anti-tumor effect, while the anti-tumor effect and molecular mechanism of gambogic acid on cervical cancer need to be studied. Our study confirms that the cytotoxic effect of gambogic acid on cervical cancer cells depends on the expression of TR3 protein. Moreover, gambogic acid-induced apoptosis requires TR3 expression. In the mechanism, gambogic acid promoted nuclear export of TR3, resulting in up-regulation of p53, which leads to the decrease of mitochondrial membrane potential, eventually inducing apoptosis. These results suggest that the nuclear export of TR3 mediated gambogic acid-induced apoptosis through a p53-dependent apoptosis pathway.
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- 2018
24. Long non-coding RNA RP11-552M11.4 favors tumorigenesis and development of cervical cancer via modulating miR-3941/ATF1 signaling
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Liang Zhao, Yunsheng Xu, Xuan Liu, Rongying Ou, Yi Ren, Jianrong Li, Wenfeng Li, Wangying Zhou, Jiangmin Lv, Cheng Zhang, and Xiangyun Li
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Carcinogenesis ,Uterine Cervical Neoplasms ,02 engineering and technology ,Biology ,medicine.disease_cause ,Biochemistry ,law.invention ,03 medical and health sciences ,Structural Biology ,law ,Cell Line, Tumor ,medicine ,Humans ,Molecular Biology ,030304 developmental biology ,Cell Proliferation ,0303 health sciences ,ATF1 ,Base Sequence ,Competing endogenous RNA ,Cell growth ,RNA ,Proteins ,General Medicine ,Middle Aged ,021001 nanoscience & nanotechnology ,medicine.disease ,eye diseases ,Long non-coding RNA ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Cancer research ,Disease Progression ,Suppressor ,Female ,RNA, Long Noncoding ,0210 nano-technology ,Ovarian cancer ,Signal Transduction - Abstract
As one of the most aggressive malignancies, cervical cancer (CC) which mainly affects females has high risks of relapse and death. Long non-coding RNA (lncRNA) RP11-552M11.4 is verified to promote the progression of ovarian cancer; nevertheless, its role and the probable molecular mechanisms in CC remain unclear until the present study. Herein, we unveiled that the expression of lncRNA RP11-552M11.4 tested by qRT-PCR was enhanced in tumor tissues compared with the para-carcinoma tissues and related to FIGO Stage, lymph node metastasis, vascular invasion and distant metastasis in CC. Additionally, CC patients with high lncRNA RP11-552M11.4 level suffered from poor clinical outcomes. Moreover, silenced lncRNA RP11-552M11.4 restrained cell proliferation, migration and invasion in CC cells. Subsequently, the mechanistic studies revealed that lncRNA RP11-552M11.4 functioned as a ceRNA of ATF1 in CC by acting as the endogenous sponge for miR-3941, which was identified as a tumor suppressor in CC. Moreover, both miR-3941 inhibition and ATF1 overexpression restored the impacts of inhibited lncRNA RP11-552M11.4 on cellular processes in CC cells. Our observations elucidated the carcinogenic role of lncRNA RP11-552M11.4 in CC was mediated through miR-3941/ATF1 axis, giving a new insight into the effective target for the treatment and prognosis of cervical cancer.
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- 2018
25. MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway
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Qin He, Rongying Ou, Fengxing Tao, Yunsheng Xu, Liang Zhao, and Yiyi Lu
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0301 basic medicine ,Cancer Research ,miR-218-5p ,Cell ,Biology ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,Gentamicin protection assay ,LYN ,microRNA ,Genetics ,medicine ,lcsh:QH573-671 ,NF-κB signaling pathway ,lcsh:Cytology ,Microarray analysis techniques ,Cell growth ,Cell migration ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Cervical cancer ,Cancer research ,Signal transduction - Abstract
Background We are committed to investigate miR-218-5 effects on the progression of cervical cancer (CC) cell and find out the molecular mechanism. Methods GSE9750 was obtained from GEO database and R Limma package was applied to filter out dysregulated genes. The pathways were enriched by GSEA software, ClusterProfiler and enrichplot packages to predict the function of DEGs. The binding sites of LYN were detected by miRanda and TargetScan. The miR2Disease database was used to find miRNAs related with CC. The expression of miR-218-5p and LYN were quantified by qRT-PCR and that of LYN protein was measured by western blot. The targeted relationships between miR-218-5p and LYN were verified by dual-luciferase reporter assay. Colony formation assays, wound healing, transwell invasion assay and flow cytometer analysis were performed to investigate the roles that miR-218-5p and LYN played in migration, invasion and death of cervical carcinoma. Xenografts established in nude mice were used to assess tumor growth in vivo. Results The highly expressed mRNA LYN was selected by microarray analysis in GSE9750. NF-κB signaling pathway was enriched base on GSEA results. The expression of miR-218-5p was lower but LYN was higher in CC primary tumors compared with normal control. In addition, miR-218-5p could regulate the expression of LYN in HeLa cells negatively. Overexpression of LYN could promote cell migration and invasion, but inhibit cell death in vitro, and also promote tumor formation in vivo via activating NF-κB signaling pathway which could be reversed by miR-218-5p. Conclusions MiR-218-5p suppressed the progression of CC via LYN/NF-κB signaling pathway.
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- 2018
26. Human papillomavirus type 16 E7 oncoprotein-induced upregulation of lysine-specific demethylase 5A promotes cervical cancer progression by regulating the microRNA-424–5p/suppressor of zeste 12 pathway
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Jia Liu, Yi Ren, Liang Zhao, Rongying Ou, Hongqin Zhao, Yunsheng Xu, Zhengzheng Shi, Qian Zhang, and Yuyang Zhang
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Adult ,0301 basic medicine ,Papillomavirus E7 Proteins ,Uterine Cervical Neoplasms ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,Histone methylation ,microRNA ,medicine ,SUZ12 ,Animals ,Humans ,Epigenetics ,Cell Proliferation ,Cervical cancer ,Human papillomavirus 16 ,Mice, Inbred BALB C ,biology ,Papillomavirus Infections ,Epithelial Cells ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,Neoplasm Proteins ,Tumor Burden ,MicroRNAs ,030104 developmental biology ,Gene Expression Regulation ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,KDM5A ,Host-Pathogen Interactions ,Disease Progression ,biology.protein ,Cancer research ,Demethylase ,Female ,Retinoblastoma-Binding Protein 2 ,Signal Transduction ,Transcription Factors - Abstract
Human papillomavirus (HPV) infection and viral protein expression cause several epigenetic alterations that lead to cervical carcinogenesis. Our previous study identified that upregulated lysine-specific demethylase (KDM) 2 A promotes cervical cancer progression by inhibiting mircoRNA (miR)-132 function. However, the roles of histone methylation modifiers in HPV-related cervical cancer remain unclear. In the present study, changes in the expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E6/E7 in CaSki cells. The dysregulated expression of KDM5A was identified, and its function in cervical cancer was investigated in vitro and in vivo. E7 oncoprotein-induced upregulation of KDM5A promoted cervical cancer cell proliferation and invasiveness in vitro and in vivo, which was correlated with poor prognosis in patients with cervical cancer. KDM5A was found to physically interact with the promoter region of miR-424–5p, and to suppress its expression by removing the tri- and di-methyl groups from H3K4 at the miR-424–5p locus. Furthermore, miR-424–5p repressed cancer cell proliferation and invasiveness by targeting suppressor of zeste 12 (Suz12). KDM5A upregulation promoted cervical cancer progression by repressing miR-424–5p, which resulted in a decrease in Suz12. Therefore, KDM5A functions as a tumor activator in cervical cancer pathogenesis by binding to the miR-424–5p promoter and inhibiting its tumor-suppressive function. These results indicate a function for KDM5A in cervical cancer progression and suggest its candidacy as a novel prognostic biomarker and target for the clinical management of this malignancy.
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- 2020
27. The value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography in asymptomatic examinees with unexplained elevated blood carcinoembryonic antigen levels
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Rongying Ou, Xiangwu Zheng, Wenfeng Li, Lingling Xiong, Dezhi Cheng, Ting Chen, Liang Zhao, Weiwei Yin, Deyao Xie, and Yunsheng Xu
- Subjects
Adult ,Male ,medicine.medical_specialty ,Population ,Multimodal Imaging ,Asymptomatic ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Carcinoembryonic antigen ,Fluorodeoxyglucose F18 ,Neoplasms ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Risk factor ,education ,Aged ,Asymptomatic Diseases ,education.field_of_study ,medicine.diagnostic_test ,biology ,business.industry ,Cancer ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Carcinoembryonic Antigen ,Positron emission tomography ,Positron-Emission Tomography ,030220 oncology & carcinogenesis ,biology.protein ,Female ,Radiology ,Radiopharmaceuticals ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Nuclear medicine - Abstract
Cancer is still a clinical challenge, with many efforts invested in order to achieve timely detection. Unexplained elevated blood carcinoembryonic antigen levels are occasionally observed in an asymptomatic population and considered as a risk factor of cancers. The purpose of this study was to determine the validity of 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) for detecting cancer in an asymptomatic population with an unexplained elevation in blood carcinoembryonic antigen (CEA) levels.This retrospective study included a total of 1920 asymptomatic examinees conducted from August 2011 through September 2013. The participants underwent CEA assay and conventional medical imaging (CEA-conventional), or CEA assay and F-18 FDG-PET/CT (CEA-PET/CT). The validity of conventional medical imaging and CEA-PET/CT scanning for detecting cancer and early-stage cancer in an asymptomatic population with an unexplained elevation in blood CEA levels were evaluated.Sensitivity, specificity, cancer detection rate, missed cancer detection rate, early-stage cancer detection rate, and early-stage cancer ratio using the CEA-PET/CT scanning were 96.6 %, 100 %, 10.4 %, 0.4 %, 3.7 %, and 34.5 %, respectively. In contrast, the corresponding values obtained using the conventional medical imaging were 50.6 % (P 0.0001), 100 % (P 0.9999), 50.6 % (P 0.0001), 99.9 % (P = 0.055), 2.6 % (P 0.0001), 2.5 % (P = 0.04), 0.7 % (P = 0.0004), and 14.5 % (P = 0.002), respectively.The F-18 FDG-PET/CT scanning significantly improved the validity of the cancer detection program in the asymptomatic population with an unexplained elevation in CEA levels.
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- 2015
28. Casiopeina II‑gly acts on lncRNA MALAT1 by miR‑17‑5p to inhibit FZD2 expression via the Wnt signaling pathway during the treatment of cervical carcinoma
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Rongying Ou, Qianwen Zhang, Li Zhu, Fan Lin, Liang Zhao, Yunsheng Xu, and Fangfang Huang
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0301 basic medicine ,Cancer Research ,Messenger RNA ,Frizzled ,MALAT1 ,Oncogene ,Chemistry ,Wnt signaling pathway ,frizzled class receptor 2 ,General Medicine ,Articles ,microRNA-17-5p ,Molecular biology ,metastasis associated lung adenocarcinoma transcript 1 ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Casiopeina II-gly ,030220 oncology & carcinogenesis ,microRNA ,Gene expression ,Viability assay ,cervical carcinoma - Abstract
The present study investigated the underlying regulatory network involved in the differential expression of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non‑coding (lnc)RNA, microRNA‑17‑5p (miR‑17‑5p) and frizzled class receptor 2 (FZD2) mRNA under the influence of Casiopeina II‑gly (Cas‑II‑gly) via the Wnt signaling pathway in cervical carcinoma (CC). The gene expression data were obtained from the Gene Expression Omnibus database (https://www.ncbi.nlm.nih.gov/geo/), and the differentially expressed genes were determined using R software. The R ClusterProfiler and enrichplot packages were applied for gene‑set enrichment analysis based on the Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes databases. TargetScan and the starBase database were used to predict the targeting associations between the miRNAs and lncRNAs/mRNAs. The MALAT1/miR‑17‑5p/mRNA FZD2 expression levels were measured via reverse transcription‑quantitative polymerase chain reaction. The protein expression was monitored by western blot analysis. The target association among the lncRNA MALAT1, miR‑17‑5p and FZD2 was validated via a dual luciferase reporter assay. Cell viability and apoptosis were determined via MTT assays, EdU staining and flow cytometry. The results indicated that the expression levels of lncRNA MALAT1 and FZD2 mRNA were downregulated, while miR‑17‑5p expression was upregulated in HeLa and CaSki cells treated with increasing Cas‑II‑gly concentrations. The cell viability was decreased, and the apoptosis rate was increased in HeLa and CaSki cells following Cas‑II‑gly treatment. Furthermore, western blot analysis results demonstrated that Cas‑II‑gly and the MALAT1/miR‑17‑5p/FZD2 axis could affect the expression of proteins associated with the Wnt signaling pathway, including disheveled segment polarity protein, glycogen synthase kinase‑3β and β‑catenin, and via the MALAT1/miR‑17‑5p/FZD2/Wnt signaling pathway axis.
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- 2018
29. MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via
- Author
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Yunsheng, Xu, Qin, He, Yiyi, Lu, Fengxing, Tao, Liang, Zhao, and Rongying, Ou
- Subjects
miR-218-5p ,Cervical cancer ,Primary Research ,LYN ,NF-κB signaling pathway - Abstract
Background We are committed to investigate miR-218-5 effects on the progression of cervical cancer (CC) cell and find out the molecular mechanism. Methods GSE9750 was obtained from GEO database and R Limma package was applied to filter out dysregulated genes. The pathways were enriched by GSEA software, ClusterProfiler and enrichplot packages to predict the function of DEGs. The binding sites of LYN were detected by miRanda and TargetScan. The miR2Disease database was used to find miRNAs related with CC. The expression of miR-218-5p and LYN were quantified by qRT-PCR and that of LYN protein was measured by western blot. The targeted relationships between miR-218-5p and LYN were verified by dual-luciferase reporter assay. Colony formation assays, wound healing, transwell invasion assay and flow cytometer analysis were performed to investigate the roles that miR-218-5p and LYN played in migration, invasion and death of cervical carcinoma. Xenografts established in nude mice were used to assess tumor growth in vivo. Results The highly expressed mRNA LYN was selected by microarray analysis in GSE9750. NF-κB signaling pathway was enriched base on GSEA results. The expression of miR-218-5p was lower but LYN was higher in CC primary tumors compared with normal control. In addition, miR-218-5p could regulate the expression of LYN in HeLa cells negatively. Overexpression of LYN could promote cell migration and invasion, but inhibit cell death in vitro, and also promote tumor formation in vivo via activating NF-κB signaling pathway which could be reversed by miR-218-5p. Conclusions MiR-218-5p suppressed the progression of CC via LYN/NF-κB signaling pathway.
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- 2018
30. Exploration of the molecular mechanisms of cervical cancer based on mRNA expression profiles and predicted microRNA interactions
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Zhechao Zhang, Liang Zhao, Hongyan Lou, Rongying Ou, Xiao-Jian Yan, Jingjing Liang, Wen-Feng Li, and Yunsheng Xu
- Subjects
0301 basic medicine ,differentially expressed genes ,Cancer Research ,microRNA ,Oncogene ,cervical cancer ,Cancer ,Articles ,Cell cycle ,Biology ,medicine.disease ,Molecular medicine ,survival analysis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,CDKN2A ,030220 oncology & carcinogenesis ,Cancer cell ,Cancer research ,medicine ,CHEK1 - Abstract
The molecular mechanisms of cervical cancer have been minimally explored with multi-omics data. In the present study, mRNA expression profiles were analyzed and combined with predicted miRNA interactions to contribute to the characterization of the underlying regulatory mechanisms of cervical cancer. A total of 92 significantly differentially expressed genes (DEGs) were identified in 33 tumor samples by comparison with 29 normal samples. mRNA-miRNA interaction network analysis revealed that 16 out of the 92 DEGs, including checkpoint kinase 1 (CHEK1), SRY-box 17 (SOX17), centrosomal protein 55, cyclin dependent kinase inhibitor 2A (CDKN2A), and inhibitor of DNA binding 4, were the targets of 4 miRNAs which were previously reported to be involved in the regulation of cervical cancer. Tumor and normal samples could be distinctly classified into two groups based on the expression of the 16 DEGs. Furthermore, survival analysis using the SurvExpress database indicated that the 16 DEGs could individually significantly differentiate low- and high-risk cervical cancer groups. Overall, multiple biological processes are likely to participate in the progression of cervical cancer based on the pathway and function enrichment identified for the DEGs. The dysregulation of SOX17 is associated with the regulation of embryonic development, the determination of cell fate and likely promotes cancer cell transformation. The dysregulation of CHEK1 and CDKN2A further promote cancer cell proliferation by affecting the cell cycle checkpoint in response to DNA damage. The identification of critical genes and biological processes associated with cervical cancer may be beneficial for the exploration of the molecular mechanisms.
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- 2018
31. Up-regulated BCAR4 contributes to proliferation and migration of cervical cancer cells
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Hua Zhu, Shi Li, Xiangjian Chen, Ruanmin Zou, Rongying Ou, Jisen Xue, Yan Hu, Xuejing Jin, Lulu Chen, and Xiao-Jian Yan
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0301 basic medicine ,Uterine Cervical Neoplasms ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Downregulation and upregulation ,Cell Movement ,medicine ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Gene silencing ,Humans ,Clinical significance ,Neoplasm Invasiveness ,Cell Proliferation ,Cervical cancer ,business.industry ,Middle Aged ,medicine.disease ,Prognosis ,Gene Expression Regulation, Neoplastic ,Survival Rate ,030104 developmental biology ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Case-Control Studies ,Cancer research ,Disease Progression ,Biomarker (medicine) ,Surgery ,Female ,RNA, Long Noncoding ,business ,Follow-Up Studies - Abstract
OBJECTIVES Recently, thousands of long non-coding RNAs (lncRNAs) involved in development and metastasis of malignant tumors have been identified. Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) has been proved to promote proliferation and metastasis in multiple tumors. However, the function and significance of BCAR4 in cervical cancer are still unclear. METHODS In this study, we concentrated on the biological function and clinical significance of BCAR4 in cervical cancer. More specifically, BCAR4 expression was evaluated in cervical cancer tissues and cell lines by qRT-PCR. Moreover, the prognostic factors were assessed by Kaplan-Meier analysis and Cox proportional hazards models. Additionally, functional assays were conducted and the potential mechanism was explored. RESULTS Our study showed that BCAR4 expression was significantly up-regulated in cervical cancer tissue and cell lines. Moreover, patients with high BCAR4 expression showed worse survival outcomes and overexpression of BCAR4 might be an independent prognostic factor in cervical cancer. Furthermore, overexpression of BCAR4 remarkably promoted the proliferation, motility of cervical cancer cells and silencing BCAR4 significantly suppressed the proliferation, migration and invasion of cervical cancer cells. Additionally, overexpression of BCAR4 promoted epithelial-mesenchymal transition (EMT) process and silencing BCAR4 suppressed EMT process in cervical cancer cells. CONCLUSIONS The results indicated that BCAR4 might play a crucial role in cervical cancer progression and act as an underlying biomarker for the diagnosis and prognosis of cervical cancer.
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- 2018
32. K-Ras promotes the non-small lung cancer cells survival by cooperating with sirtuin 1 and p27 under ROS stimulation
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Liang Zhao, Han Yang, Rongying Ou, Gang Li, Dezhi Cheng, Yunsheng Xu, and Wenfeng Li
- Subjects
MAPK/ERK pathway ,MAP Kinase Signaling System ,Regulator ,Proto-Oncogene Proteins p21(ras) ,Mice ,Sirtuin 1 ,Cyclin-dependent kinase ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Lung cancer ,biology ,Smoking ,Acetylation ,Cell Cycle Checkpoints ,General Medicine ,Cell cycle ,medicine.disease ,Xenograft Model Antitumor Assays ,Cell biology ,Gene Expression Regulation, Neoplastic ,Tumor progression ,biology.protein ,Signal transduction ,Reactive Oxygen Species ,Cyclin-Dependent Kinase Inhibitor p27 - Abstract
Cigarette smoking might lead to lung cancer. However, the related signaling pathways at molecular level remained unknown until now. In this study, we studied the signaling processes associated between tobacco exposure and lung cancer. First, we detected and validated pathway-specific gene expression at bronchial epithelium. These proteins reflected the activation of signaling pathways relevant to tobacco exposure, including ATM, BCL2, GPX1, K-Ras, IKBKB, and SIRT1. Tobacco smoking was simulated via reactive oxygen species (ROS) pathway. ROS not only arrested cell cycle at G1/S stage but also increased expressions of Sirt1 and p27. Further studies showed that the expression of p27 was dependent on ERK1/2 activation, and p27 itself could halt cell cycle by inhibiting the activation of CDKs. Moreover, activation of K-Ras, the key regulator of Ras/ERK pathway, was tightly regulated by enzyme activity of Sirt1. Deacetylation of K-Ras by Sirt1 increased the transformation of Ras-GTP to Ras-GDP, promoting the activation of downstream of ERK1/2. In reverse, Ras/ERK pathway could also regulate Sirt1 transcription. In conclusion, inhibition of Sirt1 may be an effective strategy for the prevention of tumor progression in high-risk patients or as a therapeutic strategy in established tumors.
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- 2015
33. miR-133a acts as a tumor suppressor in colorectal cancer by targeting eIF4A1
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Yiyi Lu, Rongying Ou, Wenfeng Li, Lingling Xiong, Anqi Chen, Fengxing Tao, Yunsheng Xu, Liang Zhao, Qin He, and Ting Chen
- Subjects
0301 basic medicine ,Colorectal cancer ,Cell Survival ,Biology ,medicine.disease_cause ,Colony-Forming Units Assay ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Movement ,microRNA ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,RC254-282 ,Cell Proliferation ,Oncogene ,Cell growth ,Tumor Suppressor Proteins ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,General Medicine ,medicine.disease ,HCT116 Cells ,Primary tumor ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Eukaryotic Initiation Factor-4A ,Cancer research ,Ectopic expression ,Carcinogenesis ,Colorectal Neoplasms - Abstract
Emerging evidence indicates that microRNAs play critical roles in carcinogenesis and cancer progression. In this study, miR-133a was found to be significantly downregulated in colon tumor tissues. We aimed to determine its biological function, molecular mechanisms, and direct target genes in colorectal cancer. From these results, we found that miR-133a was significantly downregulated in primary tumor tissues and colon cancer cell lines. Ectopic expression of miR-133a in colon cancer cell lines significantly suppressed cell growth, as evidenced by cell viability and colony formation assays, as well as reduced xenograft tumor growth in nude mice. However, the effect of miR-133a was abolished by the overexpression of eIF4A1. Moreover, miR-133a inhibited cellular migration and invasiveness. A luciferase activity assay revealed oncogene eukaryotic translation initiation factor 4A1 as a direct target gene of miR-133a, whose expression was inversely correlated with that of miR-133a. Our results demonstrate that miR-133a plays a pivotal role in colorectal cancer by inhibiting cell proliferation, invasion, and migration by targeting oncogenic eukaryotic translation initiation factor 4A1, which acts as a tumor suppressor and may provide a new potential therapeutic target in colorectal cancer.
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- 2017
34. Cytolytic Activity of the Human Papillomavirus Type 16 E711-20Epitope-Specific Cytotoxic T Lymphocyte Is Enhanced by Heat Shock Protein 110 inHLA-A*0201Transgenic Mice
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Rongying Ou, Jun Tang, Zhenzhen Ding, Yunsheng Xu, and Bing Ni
- Subjects
Cytotoxicity, Immunologic ,Microbiology (medical) ,Papillomavirus E7 Proteins ,Clinical Biochemistry ,Immunology ,Epitopes, T-Lymphocyte ,Mice, Transgenic ,Biology ,Immunoadjuvant ,Epitope ,Mice ,Immune system ,Adjuvants, Immunologic ,Antigen ,Heat shock protein ,HLA-A2 Antigen ,Splenocyte ,Animals ,Humans ,Immunology and Allergy ,Cytotoxic T cell ,Papillomavirus Vaccines ,HSP110 Heat-Shock Proteins ,Vaccines ,Immunogenicity ,Cytotoxicity Tests, Immunologic ,Molecular biology ,Mice, Inbred C57BL ,Female ,T-Lymphocytes, Cytotoxic - Abstract
Heat shock proteins (HSPs) have been successfully applied to a broad range of vaccines as biological adjuvants to enhance the immune response. The recently defined HSP110, in particular, exhibits strong protein binding affinity and is capable of enhancing the immunogenicity of protein antigens remarkably more than other HSP family members. In our previous study, we verified that murine HSP110 (mHSP110) significantly enhanced the immune response of a C57BL/6 mouse model to the H-2d-restricted human papillomavirus (HPV) E749-57epitope (short peptide spanning the 49th to 57th amino acid residues in the E7 protein). To determine whether HSP110 similarly enhances the immunogenicity of human epitope peptides, we used theHLA-A2transgenic mouse model to investigate the efficacy of the mHSP110 chaperone molecule as an immunoadjuvant of the human HLA-A2-restricted HPV16 E711-20epitope vaccine. Results showed that mHSP110 efficiently formed a noncovalently bound complex with the E711-20epitope. The mHSP110-E711-20complex induced epitope-specific splenocyte proliferation and E711-20-specific gamma interferon (IFN-γ) secretion. Importantly, cytotoxic T lymphocytes primed by the mHSP110-E711-20complex exerted strong cytolytic effects on target T2cells pulsed with the E711-20peptide or TC-1 cells transfected with theHLA-A2gene. In addition, the mHSP110-E711-20complex elicited strongerex vivoandin vivoantitumor responses than either emulsified complete Freund's adjuvant or HSP70-chaperoned E711-20peptide. These collective data suggest that HSP110 is a promising immunomodulator candidate for peptide-based human cancer vaccines, such as for the HLA-A2-restricted E711-20epitope.
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- 2013
35. MicroRNA-329-3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer
- Author
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Liang Zhao, Rongying Ou, Jingjing Liang, Yunsheng Xu, Hongyan Lou, Zhechao Zhang, and Wenfeng Li
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Uterine Cervical Neoplasms ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Internal medicine ,Cell Line, Tumor ,microRNA ,medicine ,Gene silencing ,Humans ,Aged ,Cell Proliferation ,Cervical cancer ,Mitogen-Activated Protein Kinase 1 ,Oncogene ,Cancer ,General Medicine ,Cell cycle ,Middle Aged ,medicine.disease ,Molecular medicine ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Female ,Carcinogenesis - Abstract
Cervical cancer is the second most common gynecological cancer worldwide and remains as one of the leading causes of cancer-related death among women. Despite great progress in the treatment of cervical cancer, the 5-year overall survival rate for patients with this disease remains unsatisfactory. Over the past decade, an increasing number of studies indicate a central role for microRNAs in the initiation and progression of cervical cancer. microRNA‑329-3p (miR-329-3p) has been studied in many types of human cancer; however, the expression level, biological role and the underlying mechanism of miR-329-3p in cervical cancer has not yet been investigated. In the present study, we found that the expression levels of miR-329-3p were reduced in both cervical cancer tissues and cell lines. Low miR-329-3p expression was negatively correlated with histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastasis of cervical cancer patients. In addition, upregulation of miR‑329-3p suppressed cell proliferation, migration and invasion of cervical cancer. Furthermore, MAPK1 was identified as a direct target gene of miR-329-3p. MAPK1 was significantly upregulated in cervical cancer tissues and was inversely correlated with miR-329-3p expression in the cervical cancer tissues. Silencing of MAPK1 by RNA interference mimicked the effects of miR-329-3p overexpression on cell proliferation, migration and invasion in cervical cancer. Moreover, rescue experiments showed that restoration of the expression of MAPK1 reversed the effects of miR‑329-3p overexpression in cervical cancer cells. Taken together, these findings suggest that miR-329-3p has a critical tumor-suppressive roles by directly targeting MAPK1 in cervical cancer, and it may be investigated as a novel therapeutic target for the treatment of patients with this disease.
- Published
- 2016
36. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice
- Author
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Rongying Ou, Li Zhu, Jia Liu, Yunsheng Xu, Mingfen Lv, Liang Zhao, Jingying Wang, and Jinmeng Wang
- Subjects
0301 basic medicine ,Blood Glucose ,medicine.medical_specialty ,Neutrophils ,Endocrinology, Diabetes and Metabolism ,Population ,Inflammation ,Mitochondrion ,AMP-Activated Protein Kinases ,medicine.disease_cause ,Diet, High-Fat ,Proinflammatory cytokine ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Endocrinology ,AMP-activated protein kinase ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,medicine ,Animals ,adipocyte protein 2 ,Phosphorylation ,education ,Chemokine CCL2 ,education.field_of_study ,biology ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Fatty liver ,Body Weight ,NF-kappa B ,medicine.disease ,Oxidative Stress ,030104 developmental biology ,Liver ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,medicine.symptom ,Oxidative stress ,Signal Transduction - Abstract
Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.
- Published
- 2016
37. Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752
- Author
-
Jian-Ge Qiu, Rongying Ou, Zhen-Zhen Zheng, Zhang Wenji, Yang Yang, Zhi Shi, Xiao-Jian Yan, Qi-Wei Jiang, Feng-Feng Xie, Li-Hua Gong, Jin-Yan Chen, Xiao-Xiu Huang, Hua Zhu, and Xiu-Xiu Chen
- Subjects
0301 basic medicine ,Combination therapy ,Down-Regulation ,Mice, Nude ,Apoptosis ,X-Linked Inhibitor of Apoptosis Protein ,Pharmacology ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Basic Helix-Loop-Helix Transcription Factors ,Benzene Derivatives ,Animals ,Humans ,Sulfones ,Receptor, Notch1 ,Cell Proliferation ,Cisplatin ,Homeodomain Proteins ,Ovarian Neoplasms ,Mice, Inbred BALB C ,Dose-Response Relationship, Drug ,business.industry ,Cell growth ,Obstetrics and Gynecology ,Cancer ,Drug Synergism ,Proto-Oncogene Proteins c-mdm2 ,Cell Cycle Checkpoints ,Cell cycle ,medicine.disease ,XIAP ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Transcription Factor HES-1 ,Female ,Amyloid Precursor Protein Secretases ,Propionates ,business ,Ovarian cancer ,medicine.drug - Abstract
Objective Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. Methods Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). Results MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Conclusion Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer.
- Published
- 2015
38. Heat shock protein 110 improves the anti-tumor effects of the cytotoxic T lymphocyte epitope E7 in mice
- Author
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Bingxu Li, Yuzhang Wu, Yunsheng Xu, Zhenzhen Ding, Faliang Ren, Bing Ni, Liwei Mao, Zhiqiang Tian, Xueqi Zhang, Zhengcai Jia, Rongying Ou, and Jun Tang
- Subjects
Pharmacology ,Cancer Research ,medicine.medical_treatment ,Immunogenicity ,Immunotherapy ,Biology ,Immunoadjuvant ,Epitope ,Immune system ,Oncology ,Antigen ,Heat shock protein ,Immunology ,Peptide vaccine ,medicine ,Molecular Medicine - Abstract
Several strategies have been used to enhance the vaccine-induced immunity of peptide vaccines and effective therapeutic benefits, including the utilization of heat shock proteins (HSP), especially the HSP70 family. HSP110 exhibits a higher binding affinity with protein and is capable of enhancing the immunogenicity of protein antigens; however, whether HSP110 can also increase the efficiency of peptide vaccine remains unclear. Here, we investigated mHSP110 as a chaperone immunoadjuvant to enhance the immune response to HPV16 oncoprotein E7-derived CTL epitope E7(49-57) in a mouse model. We developed the HSP110-E7(49-57) complex and demonstrated that mHSP110 could form complexes with peptide E7(49-57) using FITC-labeled E7(49-57) as the tracer. Inoculation of the mHSP110-E7(49-57) complex was capable of priming strong epitope-specific immune response as determined by its ability to elicit an epitope-specific splenocytes proliferation and a cytotoxic T cell response, and IFNgamma production in splenocytes. Results also showed that immunization with the mHSP110-E7(49-57) complex completely protected mice against subsequent challenge with tumor cells. More importantly, immunization of this complex also significantly inhibited the growth of established tumors and prolonged the survival time of the tumor-bearing animals. Thus, mHSP110-E7(49-57) complex vaccine represents a potentially powerful approach for use in the immunotherapy of cervical cancer associated with HPV16 infection. More importantly, the multi-epitopes derived from E7 and other E proteins can be applied to the strategy described in this study to form a multi-antigenic vaccine to induce an improved antitumor immune response to cervical cancer in the future.
- Published
- 2010
39. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) Downregulates the Expression of Protumor Factors Cyclooxygenase-2 and Inducible Nitric Oxide Synthase in a GM-CSF Receptor-Independent Manner in Cervical Cancer Cells
- Author
-
Nanyan Jiang, Zhiqiang Tian, Yunsheng Xu, Rongying Ou, and Jun Tang
- Subjects
Adult ,medicine.medical_specialty ,Article Subject ,Immunology ,Down-Regulation ,Gene Expression ,Nitric Oxide Synthase Type II ,Uterine Cervical Neoplasms ,In Vitro Techniques ,Downregulation and upregulation ,Internal medicine ,Cell Line, Tumor ,Gene expression ,medicine ,lcsh:Pathology ,Humans ,Aged ,Cervical cancer ,biology ,GM-CSF Receptor ,Granulocyte-Macrophage Colony-Stimulating Factor ,Cell Biology ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Nitric oxide synthase ,Granulocyte macrophage colony-stimulating factor ,Endocrinology ,Cell culture ,Cyclooxygenase 2 ,Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ,Cancer research ,biology.protein ,Female ,medicine.drug ,lcsh:RB1-214 ,Research Article - Abstract
Enhanced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) is associated with the pathogenic processes of various tumor types. COX-2 and iNOS expression in the immunomodulatory dendritic cells is mediated by the granulocyte macrophage-colony stimulating factor (GM-CSF), which is also expressed by cervical cancer cells; however, whether and how GM-CSF regulates COX-2 and iNOS expression in clinical cervical cancer cells remain unknown. In this study, we found that the COX-2 and iNOS expression was upregulated in the cervical cancer tissues and positively correlated with cancer metastasis and stage. About one-half of the cervical cancer tissues showed strong/moderate GM-CSF expression, while the normal cervical tissues showed >80% positive rate; no GM-CSFR protein was detectable on the cervical cancer cells. The GM-CSF expression was negatively correlated with the COX-2 and iNOS expression in the cervical cancer tissues and the functional negative regulatory effect of GM-CSF on COX-2/iNOS expression was demonstrated in various cervical cancer cell lines. Therefore, in cervical cancer cells, GM-CSF might contribute an antitumor response by inhibiting iNOS and COX-2 expression in a GM-CSFR independent manner.
- Published
- 2015
40. Enhanced anti-tumor effects of HPV16E7(49-57)-based vaccine by combined immunization with poly(I:C) and oxygen-regulated protein 150
- Author
-
Bing Ni, Rongying Ou, Jun Tang, Yuzhang Wu, Jennifer C. van Velkinburgh, Yunsheng Xu, Shisheng Chen, and Xiufang Deng
- Subjects
Cancer Research ,Epidemiology ,medicine.medical_treatment ,Papillomavirus E7 Proteins ,Uterine Cervical Neoplasms ,Lymphocyte proliferation ,Lymphocyte Activation ,Cancer Vaccines ,chemistry.chemical_compound ,Mice ,Immune system ,In vivo ,Interferon ,Heat shock protein ,medicine ,Cytotoxic T cell ,Animals ,Humans ,HSP70 Heat-Shock Proteins ,Vaccines, Combined ,Human papillomavirus 16 ,business.industry ,Papillomavirus Infections ,Vaccination ,Proteins ,Neoplasms, Experimental ,Molecular biology ,Xenograft Model Antitumor Assays ,Peptide Fragments ,Mice, Inbred C57BL ,Disease Models, Animal ,Poly I-C ,Oncology ,chemistry ,Polyinosinic:polycytidylic acid ,Cancer research ,Female ,business ,Adjuvant ,medicine.drug ,T-Lymphocytes, Cytotoxic - Abstract
Background : It is well known that both heat shock protein (HSP) and Toll-like receptor (TLR)3 agonist polyinosinic:polycytidylic acid (poly(I:C)) are capable of promoting the antigen-specific immune responses. In the current study, we assessed whether the anti-tumor effects of the HPV16E7 49–57 -based vaccine can be elevated by combined applications of poly(I:C) and oxygen-regulated protein 150 (ORP150) in a mouse cervical cancer model. Methods : Recombinant mouse ORP150 and HPV E7 49–57 peptide were combined to passively form the ORP150–E7 49–57 complex under heat shock conditions. The effects of ORP150–E7 49–57 complex plus poly(I:C) adjuvant on lymphocyte proliferation and functional cytotoxic T cells were investigated by methyl thiazolyl tetrazolium (MTT), ELISPOT, and non-radioactive cytotoxicity assays. Finally, the complex's therapeutic anti-tumor effects with and without adjuvant therapy were observed in a tumor challenge experiment. Results : This combination vaccine approach significantly enhanced the proliferation of splenocytes and induced strong E7 49–57 -specific CTL responses. More importantly, the ORP150–E7 49–57 complex plus poly(I:C) vaccine format demonstrated more potent anti-tumor effects than ORP150–E7 49–57 complex alone or E7 49–57 plus poly(I:C) in TC-1 tumor-bearing mice. Conclusion : Both poly(I:C) and ORP150 chaperone can synergistically enhance the anti-tumor effects of the HPV16E7 49–57 -based vaccine in vitro and in vivo. This strategy provides a platform for the design of a tumor therapeutic vaccine capable of inducing an effective anti-tumor immune response.
- Published
- 2012
41. Modeling and predicting interactions between the human amphiphysin SH3 domains and their peptide ligands based on amino acid information
- Author
-
Li Yang, Zhihua Lin, Rongying Ou, Jianfeng Cai, Mao Shu, and Yun-Sheng Xu
- Subjects
Steric effects ,Quantitative structure–activity relationship ,Stereochemistry ,Protein Conformation ,Quantitative Structure-Activity Relationship ,Peptide ,Nerve Tissue Proteins ,Ligands ,Biochemistry ,SH3 domain ,src Homology Domains ,Structural Biology ,Drug Discovery ,Humans ,Amino Acid Sequence ,Amino Acids ,Molecular Biology ,Peptide ligand ,Pharmacology ,chemistry.chemical_classification ,Hydrogen bond ,Chemistry ,Organic Chemistry ,Hydrogen Bonding ,General Medicine ,Amino acid ,Amphiphysin ,Molecular Medicine ,Oligopeptides - Abstract
In this paper, VHESH, which was a novel set of amino acid descriptors including hydrophobic, electronic, steric, and hydrogen bond contribution properties, were proposed to characterize the structures of the decapeptides binding the human amphiphysin-1 Src homology 3 (SH3) domains, and QSAR model was constructed by partial least square (PLS) with genetic algorithm-variable selection. It was found that diversified properties of the residues between P2 and P−3 (including P2 and P−3) of the decapeptide (P4P3P2P1P0P−1P−2P−3P−4P−5) may contribute remarkable effect to the interactions between the SH3 domain and decapeptides. Particularly, hydrogen bond and steric properties of P2 and electronic properties, steric properties of P−3 may provide relatively large positive contributions to the interactions. Based on the GA-PLS model, a series of decapeptides, with relatively high binding affinities were designed. These results showed that VHESH descriptors can well represent the decapeptides. Furthermore, the model obtained, which showed low computational complexity, correlated VHESH descriptors with the binding affinities as well as that VHESH may also be applied in QSAR studies of peptides. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.
- Published
- 2010
42. Heat shock protein 110 improves the antitumor effects of the cytotoxic T lymphocyte epitope E7(49-57) in mice
- Author
-
Faliang, Ren, Yunsheng, Xu, Liwei, Mao, Rongying, Ou, Zhenzhen, Ding, Xueqi, Zhang, Jun, Tang, Bingxu, Li, Zhengcai, Jia, Zhiqiang, Tian, Bing, Ni, and Yuzhang, Wu
- Subjects
Human papillomavirus 16 ,Papillomavirus E7 Proteins ,Papillomavirus Infections ,Vaccination ,Uterine Cervical Neoplasms ,Viral Vaccines ,Cancer Vaccines ,Xenograft Model Antitumor Assays ,Peptide Fragments ,Recombinant Proteins ,Specific Pathogen-Free Organisms ,Mice, Inbred C57BL ,Epitopes ,Mice ,Adjuvants, Immunologic ,Cell Line, Tumor ,Animals ,Humans ,Female ,HSP110 Heat-Shock Proteins ,Antigens, Viral ,Protein Binding ,T-Lymphocytes, Cytotoxic - Abstract
Several strategies have been used to enhance the vaccine-induced immunity of peptide vaccines and effective therapeutic benefits, including the utilization of heat shock proteins (HSP), especially the HSP70 family. HSP110 exhibits a higher binding affinity with protein and is capable of enhancing the immunogenicity of protein antigens; however, whether HSP110 can also increase the efficiency of peptide vaccine remains unclear. Here, we investigated mHSP110 as a chaperone immunoadjuvant to enhance the immune response to HPV16 oncoprotein E7-derived CTL epitope E7(49-57) in a mouse model. We developed the HSP110-E7(49-57) complex and demonstrated that mHSP110 could form complexes with peptide E7(49-57) using FITC-labeled E7(49-57) as the tracer. Inoculation of the mHSP110-E7(49-57) complex was capable of priming strong epitope-specific immune response as determined by its ability to elicit an epitope-specific splenocytes proliferation and a cytotoxic T cell response, and IFNgamma production in splenocytes. Results also showed that immunization with the mHSP110-E7(49-57) complex completely protected mice against subsequent challenge with tumor cells. More importantly, immunization of this complex also significantly inhibited the growth of established tumors and prolonged the survival time of the tumor-bearing animals. Thus, mHSP110-E7(49-57) complex vaccine represents a potentially powerful approach for use in the immunotherapy of cervical cancer associated with HPV16 infection. More importantly, the multi-epitopes derived from E7 and other E proteins can be applied to the strategy described in this study to form a multi-antigenic vaccine to induce an improved antitumor immune response to cervical cancer in the future.
- Published
- 2009
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